Integrins and anoikis

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Abstract

The loss of integrin-mediated cell—matrix contact induces apoptosis (‘anoikis’) in certain cell types. Recently it has been shown that protein kinase signaling pathways control anoikis both positively and negatively. Focal adhesion kinase, when activated by integrins, can suppress anoikis. Phosphatidylinositol 3-kinase and the AKT oncoprotein may mediate the anoikis-suppressing effects of focal adhesion kinase. Conversely, the stress-activated protein kinase/Jun amino-terminal kinase pathway promotes anoikis. Latest results indicate that caspase-mediated cleavage of the first component of this latter pathway, MEKK-1, may trigger activation of this pathway in anoikis. In addition, certain integrins may regulate bcl-2 expression levels, possibly adjusting the threshold for anoikis.

References (50)

  • L-H Xu et al.

    Attenuation of the expression of the focal adhesion kinase induces apoptosis in tumor cells

    Cell Growth Differ

    (1996)
  • E Bossy-Wetzel et al.

    Induction of apoptosis by the transcription factor c-jun

    EMBO J

    (1997)
  • F Lee et al.

    Activation of the IκBα kinase complex by MEKK-1, a kinase of the JNK pathway

    Cell

    (1997)
  • GE Hannigan et al.

    Regulation of cell adhesion and anchorage-dependent growth by a new β1-integrin-linked protein kinase

    Nature

    (1996)
  • LM Machesky et al.

    Rho: a connection between membrane receptor signalling and the cytoskeleton

    Trends Cell Biol

    (1996)
  • J Folkman et al.

    Role of cell shape in growth control

    Nature

    (1978)
  • SM Frisch et al.

    Disruption of epithelial cell-matrix interactions induces apoptosis

    J Cell Biol

    (1994)
  • JE Meredith et al.

    The extracellular matrix as a cell survival factor

    Mol Biol Cell

    (1993)
  • R Polakowska et al.

    Apoptosis in human skin development: morphogenesis, periderm and stem cells

    Dev Dyn

    (1994)
  • P Hall et al.

    Regulation of cell number in the mammalian gastrointestinal tract: the importance of apoptosis

    J Cell Sci

    (1994)
  • N Boudreau et al.

    Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix

    Science

    (1995)
  • P Vachon et al.

    Merosin and laminin in myogenesis; specific requirement for merosin in myotube stability and survival

    J Cell Biol

    (1996)
  • A Montgomery et al.

    Integrin ανβ3 rescues melanoma cells from apoptosis in three-dimensional dermal collagen

    Proc Natl Acad Sci USA

    (1994)
  • J Hungerford et al.

    Inhibition of pp125FAK in cultured fibroblasts results in apoptosis

    J Cell Biol

    (1996)
  • A Howlett et al.

    Cellular growth and survival are mediated by β1 integrins in normal human breast epithelium but not in breast carcinoma

    J Cell Sci

    (1995)
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